EP3506768A1 - Use of human milk oligosaccharides in calves fattening - Google Patents
Use of human milk oligosaccharides in calves fatteningInfo
- Publication number
- EP3506768A1 EP3506768A1 EP17755546.3A EP17755546A EP3506768A1 EP 3506768 A1 EP3506768 A1 EP 3506768A1 EP 17755546 A EP17755546 A EP 17755546A EP 3506768 A1 EP3506768 A1 EP 3506768A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- human milk
- composition
- calves
- oligosaccharide
- milk replacer
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
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- 229940050549 fiber Drugs 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 210000005095 gastrointestinal system Anatomy 0.000 description 1
- 208000018685 gastrointestinal system disease Diseases 0.000 description 1
- 235000021312 gluten Nutrition 0.000 description 1
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- FKADDOYBRRMBPP-UHFFFAOYSA-N lacto-N-fucopentaose II Natural products OC1C(O)C(O)C(C)OC1OC1C(OC2C(C(O)C(O)C(CO)O2)O)C(NC(C)=O)C(OC2C(C(OC(C(O)CO)C(O)C(O)C=O)OC(CO)C2O)O)OC1CO FKADDOYBRRMBPP-UHFFFAOYSA-N 0.000 description 1
- CMQZRJBJDCVIEY-UHFFFAOYSA-N lacto-N-fucopentaose III Natural products OC1C(O)C(O)C(C)OC1OC1C(OC2C(C(O)C(O)C(CO)O2)O)C(CO)OC(OC2C(C(OC3C(OC(O)C(O)C3O)CO)OC(CO)C2O)O)C1NC(C)=O CMQZRJBJDCVIEY-UHFFFAOYSA-N 0.000 description 1
- WMYQZGAEYLPOSX-JOEMMLBASA-N lex-lactose Chemical compound OC1[C@@H](O)[C@@H](O)[C@@H](C)O[C@@H]1O[C@H]1C(O[C@H]2[C@@H](C(O)C(O)C(CO)O2)O)[C@@H](CO)O[C@@H](O[C@@H]2[C@H]([C@H](OC(C(O)CO)[C@H](O)[C@@H](O)C=O)OC(CO)C2O)O)C1NC(C)=O WMYQZGAEYLPOSX-JOEMMLBASA-N 0.000 description 1
- 235000020786 mineral supplement Nutrition 0.000 description 1
- 229940029985 mineral supplement Drugs 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 235000021118 plant-derived protein Nutrition 0.000 description 1
- 229940117728 pre milk Drugs 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- 229940001941 soy protein Drugs 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 239000011573 trace mineral Substances 0.000 description 1
- 235000013619 trace mineral Nutrition 0.000 description 1
- 150000004043 trisaccharides Chemical class 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- QYSXJUFSXHHAJI-YRZJJWOYSA-N vitamin D3 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-YRZJJWOYSA-N 0.000 description 1
- 235000005282 vitamin D3 Nutrition 0.000 description 1
- 239000011647 vitamin D3 Substances 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 229940045997 vitamin a Drugs 0.000 description 1
- 229940021056 vitamin d3 Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/163—Sugars; Polysaccharides
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K50/00—Feeding-stuffs specially adapted for particular animals
- A23K50/10—Feeding-stuffs specially adapted for particular animals for ruminants
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K50/00—Feeding-stuffs specially adapted for particular animals
- A23K50/60—Feeding-stuffs specially adapted for particular animals for weanlings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/702—Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2250/00—Food ingredients
- A23V2250/28—Oligosaccharides
Definitions
- the present invention relates to the use of human milk oligosaccharides for feeding production animals such as calves.
- the present invention further relates to milk replacer compositions containing human milk oligosaccharides.
- Further subject matter of the present invention is a method for preventing and treating gastro- intestinal diseases, particularly gastro-intestinal infections, of young production animals, in particular calves, by administering an effective amount of one or more human milk oligosaccharides.
- gastro- intestinal diseases particularly gastro-intestinal infections
- the human milk oligosaccharides is 2'-fucosyllactose (2-FL).
- 2-FL 2'-fucosyllactose
- the raising of healthy calves is the basis for successful dairy farming.
- HMOs Human milk oligosaccharides
- WO-A-2012/158517 discloses the use of human milk oligosaccharides, in particular 2'-fucosyllactose for the promotion of growth of bacteria found in infant faeces.
- This prior art also intends to use human milk oligosaccharides as prebiotics for nutrition of diverse mammalia, however, besides growth promotion of enterobacteria, no experimental data whatsoever are presented so that the use of human milk
- oligosaccharides for feeding animals remains speculative.
- the technical problem underlying the present invention is to provide improved raising of young production annimals, in particular calves, especially through improvement of their feeding.
- the present invention relates to novel milk replacer compositions containing at least one human milk oligosaccharide.
- a "human milk oligosaccharide” is a sugar molecule composed of at least three carbohydrate entities, which sugar molecule is found in the milk or pre-milk of female humans.
- the HMO is an oligosaccharide composed of 3, 4, 5, 6, 7, 8, 9, 10 or more sugar entities, whereby oligosaccharides containing 4 or more entities may be linear or branched oligomers.
- HMOs are typically composed of the monosaccharides glucose, galactose, N- acetyglucosamine, N-acetylcalactosamine, fucose and N-acetylneuraminic acid. Most HMOs for use in the invention are based on the disaccharides lactose or N- acetyllactosamine, with those based on lactose are particularly preferred.
- Preferred human milk oligosaccharides in the context of the invention include, but are not limited to, 2'-fucoyllactose (2-FL), 3'-fucosyllactose (3-FL), 3'-sialyllactose (3-SL), 6'-sialyllactose (6-SL), lacto-N-tetraose (LNT), lacto-N-neotetraose (LNnT), lacto-N- hexaose (LNH), / ' so-lacto-N-octaose, / ' so-lacto-N-neooctaose, para-lacto-N-octaose, lacto-N-fucopentaose I (LNFP I), lacto-N-fucopentaose II (LNFP II), lacto-N- fucopentaose III (LNFP III),
- DSLNT disialyllacto-N-tetraose
- HMOs for use in the present invention are the human milk trisaccharides 3-FL and 2-FL. Recently, a biotechnological production of 2-FL has been provided (see WO-A-2010/070104) so that this basic HMO is available on an industrial scale (Jennewein Biotechnologie GmbH, Rheinbreitbach, Germany) .
- the HMO in the milk replacer composition is therefore preferably a synthetic one that has been prepared in bacterial culture, especially using genetically modified bacteria as taught in WO-A-2010/070104.
- 2-FL, in particular synthetic 2-FL as described before, and higher HMOs based on 2-FL are generally preferred in the context of the invention, and 2-FL is the most preferred HMO for the practice of the present invention.
- the present invention also relates to milk replacer compositions comprising more than one particular HMO whereby a mixture of two or more of the above-mentioned HMOs is preferred.
- Particularly preferred is a mixture of HMOs whereby one of the HMOs of the mixture is 2-FL or 3-FL, or the mixture comprises both 2-FL and 3-FL together with third, fourth, fifth etc. further HMOs.
- Most preferred in this context of the invention is a combination of 2-FL and 3-FL.
- the milk replacer composition of the invention can, of course, contain other sugars in addition to HMOs.
- lactose and N-acetyllactosamine are to be mentioned as preferred further oligosaccharides.
- a "milk replacer” or “milk replacer composition” means a nutritional composition for feeding of production animals, preferably selected from cattle, goat, sheep, pig, deer and horse, especially infant and young production animals.
- the term "milk replacer” and "milk replacer composition” according to the present invention also includes the definition pursuant to Art. 3 (2) of the Regulation (EC) No.
- milk replacer means a "compound feed administered in dry form or after dilution in a given quantity of liquid for feeding young animals as a complement to, or substitute for, post-colostral milk or for feeding young animals such as calves, lambs or kids intended for slaughter".
- the milk replacer composition of the invention thus typically contains one or more HMOs as described above together with a basic milk replacer composition.
- the term milk replacer composition according to the invention comprises the composition in dry form as well as its liquid form which is typically obtained by reconstitution of the dry composition with water.
- Basic nutritional compositions for providing the milk replacer composition of the invention are known in the art (for an overview for calf milk replacers, see, e.g., Bovine Alliance on Management and Nutrition (BAMN), 2008, A GUIDE TO CALF MILK REPLACERS, available online at
- Milk replacer compositions according to the invention thus generally comprise at least a protein and a fat source, optionally reconstituted in an aqueous liquid (in which ingredients may be present in the aqueous base in the form of suspension, emulsion and/or solution), typically in admixture with further ingredients such as carbohydrates, fiber, vitamins, mineral supplements, and further additives such as medicaments, emulsifiers, thickeners, trace elements, antioxidants and flavorings.
- Milk replacer compositions are usually categorized according to the source of their protein and/or fat constituents. Typical protein sources for milk replacer
- compositions especially for use in calf feeding, include skimmed milk powder, whey powder, and plant protein sources such as soy protein, soy flour, wheat gluten or wheat isolate.
- Fat components of milk replacers may be from animal fat or vegetable oils.
- Protein and fat levels are both important features of milk replacer compositions for use in the invention.
- Preferred protein levels in calf milk replacers typically range from about 18 to about 22% (w/w), most preferred about 20 % (w/w), and fat levels are preferably in the range of from about 10 to about 28 % (w/w), with about 18 to about 23% (w/w) fat being more preferred.
- the levels of ingredients also vary with the type of animal to be fed. For example, for breed calves the fat level typically ranges from about 13 to about 20 % (w/w), while the fat content in the milk replacer composition should be elevated to around 23 % (w/w) for fattening calves, i.e. calves intended for slaughter.
- carbohydrate to protein Of special consideration for production of milk replacer compositions is also the ratio of carbohydrate to protein.
- pure dried whey has a lactose content of about 70 % (w/w), and the protein content is about 12 % (w/w).
- the content of carbohydrates excluding the HMO content
- lactose, glucose and saccharose should preferably not exceed a value of about 50 % (w/w), so as to prevent a high passage rate leading to misfermentations in the colon (Kamphues (2004), supra).
- a typical basic milk replacer composition for use in the invention contains about 22 % (w/w) or more crude protein, about 20 % (w/w) or more crude fat, not more than about 0.15 (w/w) crude fiber, calcium in an amount of from about 0.75 % (w/w) to about 1 .75 % (w/w), at least about 0.7 % (w/w) phosphorous, at least about 20000 lU/lb Vitamin A, at least about 5000 lU/lb Vitamin D3, and about 100 lU/lb Vitamin E.
- the milk replacer composition according to the invention typically contains HMOs (which may be a single type of HMO such as 2-FL, or a mixture of 2 or more different HMOs) in an amount of from about 0.5 to 10.0 % (w/w), preferably about 1 to 5 % (w/w), most preferred 4 % (w/w), based on the total weight of the composition.
- HMOs which may be a single type of HMO such as 2-FL, or a mixture of 2 or more different HMOs
- the present invention is also directed to the use of HMOs (one ore more of HMOs) for feeding of production animals, in particular young production animals such as calves, lambkins, kids and foals.
- HMOs are particularly useful in calves fattening.
- the present invention is also directed to a method for feeding production animals, in particular young production animals such as calves, lambkins, kids and foals, comprising the step of feeding the production animal with a milk replacer composition of the invention.
- the feeding method of the invention improves the feed intake by and performance parameters of the production animals, especially in the context of calves fattening.
- a special benefit of using HMOs as an ingredient in milk replacer compositions as taught herein is an improvement of overall conditions of the fed production animals, in particular calves, lambkins, kids and foals, so that the performance parameters of the animal fed with a milk replacer according to the invention improve.
- Milk replacer compositions according to the invention decrease animal lost, especially by preventing gastro-intestinal diseases such as bacterial or viral gut infections leading to diarrhea.
- gastro-intestinal diseases such as bacterial or viral gut infections leading to diarrhea.
- the HMOs improve the growth of favorable intestinal bacteria thereby reducing the relative number of pathogenic bacteria, while at the same time prevent or at least hinder binding of pathogenic agents such as pathogenic enterobacteria and viruses to intestinal receptors.
- the HMOs are also believed to improve the animal's gut microflora, modulate muccosal immunity, and strengthen the animal's resistance against atopic conditions.
- the HMOs are particularly useful in improving the healthiness of production animals such as calves, lambkins, kids and foals.
- the HMOs (which can be either given alone or it can be provided as a mixture of HMOs, as described above) are used for prevention and treatment, and at least reduce the incidents of, gastro-intestinal diseases, in particular bacterial and viral gastro-intestinal diseases such as diarrhea (or at least shorten the periods of such diseases) in said production animals.
- the HMOs also are useful in preventing and treating atopic diseases, i.e.
- the HMOs are useful for improving the mucosal immunity of production animals, in particular those mentioned before.
- the HMOs also improve the intestinal flora of the production animals such as calves, lambkins, kids and foals.
- the HMOs can be administered alone or in form of a composition, preferably in oral administration form, which can also take the form of a milk replacer composition as defined herein.
- the medical composition can also take the form of a tablet or capsule given separately from any feeding composition.
- the invention is therefore also directed to a method for preventing or treating a gastrointestinal disease such as bacterial and viral infection in the gastro-intestinal system, for example diarrhea, in a production animal, preferably a young production animal as outlined above, comprising the step of administering a safe and effective amount of at least one HMO, or a composition containing two or more HMOs, to the production animal.
- the present invention is furthermore directed to the use of at least one HMO, or of a composition containing two or more HMOs, for the production of a medicament for the prevention or treatment of the above-mentioned conditions.
- 60 calves (Deutsche Holstein), are divided into two groups (control group and experimental group, 30 each) with equal numbers of male (15/30) and female (15/30) animals.
- the average age of the calves is 7 days. Each animal in both groups is held in single keeping. At the age of 14 days, the calves are held in the two groups with each group held in a different, but otherwise identical stable.
- the animals are fed with the milk replacer composition via an automated watering dispenser.
- the animals can take water freely from a water dispenser.
- 150 g of hay is given to each animal per day. From the 8 th week onwards, concentrated feed is given via an automated dispenser.
- Both groups, except for HMOs are fed with the same milk replacer compositions.
- the experimental group is fed with basic milk replacer composition plus 4 % (w/w) 2-FL.
- the control group is fed with additional 4 % (w/w) whey powder instead of the HMO.
- One litre of the liquid milk replacer composition contains 125 g dry milk replacer concentrate.
- Example 2 Feeding of fattening calves using milk replacer containing HMO Materials and methods: 60 calves of the breed Fleckvieh, devided into two groups (control/experimental) with 30 calves each. Equal amounts of male (15/30) and female (15/30) calves in both groups. The average age of the animals is 14 days (50 to 60 kg live weight). The animals of each group are held in a stable, both stables are identical. The animals are fed with the milk replacer composition via an automated watering dispenser. The animals can take water freely. In addition, 300 g of hay is given to each animal per day. Both groups, except for HMOs, are fed with the same milk replacer compositions.
- the experimental group is fed with basic milk replacer composition plus 4 % (w/w) 2-FL.
- the control group is fed with additional 4 % (w/w) whey powder instead of the HMO.
- one litre of the liquid feed composition contains 125 g dry milk replacer concentrate.
- concentration of the liquid feed composition is increased to 250 g per litre at the end of the experiment.
- the feeding plan is as follows:
- Duration of experiment the experiment starts at the age of ca. 14 days and ends with slaughter at a weight of ca. 230 to 240 kg (ca. 22 nd week of experiment), resulting in a duration of ca. 140 days.
- Data collection Feeding via automated dispenser with single animal recognition, measurement of food intake by each individual; hey and feed concentrate data are collected by weighing; daily weighing of each animal; sublingual measurement of body temperature at automated feeding dispenser, with rectal measurement once weekly for comparison and control; control of health condition and use of medication; weekly analysis of faeces with respect to colonisation by intestinal bacteria. After slaughtering, the body of each animal is evaluated.
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- Food Science & Technology (AREA)
- Animal Husbandry (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
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- Birds (AREA)
- Epidemiology (AREA)
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- Molecular Biology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Feed For Specific Animals (AREA)
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Abstract
Description
Claims
Applications Claiming Priority (2)
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EP16186533 | 2016-08-31 | ||
PCT/EP2017/071606 WO2018041803A1 (en) | 2016-08-31 | 2017-08-29 | Use of human milk oligosaccharides in calves fattening |
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US20020019991A1 (en) * | 1998-04-30 | 2002-02-14 | Abbott Laboratories | Compositions containing an alpha 1,2-fucose linkage and uses thereof |
US20080003329A1 (en) * | 2006-06-30 | 2008-01-03 | Ricardo Rueda | Enriched infant formulas |
JP5726751B2 (en) | 2008-12-19 | 2015-06-03 | イェネヴァイン ビオテヒノロギー ゲーエムベーハー | Synthesis of fucosylated compounds |
CA2757169A1 (en) * | 2009-04-13 | 2010-10-21 | Children's Hospital Medical Center | Milk oligosaccharide compositions and use thereof in treating infection in animals |
MX2013008500A (en) * | 2011-02-04 | 2014-03-05 | Univ California | Disialyllacto-n-tetraose (dslnt) or variants, isomers, analogs and derivatives thereof to prevent or inhibit bowel disease. |
AU2012217650B9 (en) * | 2011-02-16 | 2017-09-14 | Glycosyn LLC | Biosynthesis of human milk oligosaccharides in engineered bacteria |
US9567361B2 (en) | 2011-05-13 | 2017-02-14 | Glycosyn LLC | Use of purified 2′-fucosyllactose, 3-fucosyllactose and lactodifucotetraose as prebiotics |
NL2007931C2 (en) * | 2011-12-07 | 2013-06-10 | Friesland Brands Bv | Methods for providing sialylated oligosaccharides and products obtainable thereby. |
WO2015071401A1 (en) * | 2013-11-15 | 2015-05-21 | Nestec S.A. | Compositions for use in the prevention or treatment of necrotizing enterocolitis in infants or young children born by c-section |
US11098075B2 (en) * | 2014-09-12 | 2021-08-24 | Basf Se | Method for preparing 2′-O-fucosyllactose |
US11318175B2 (en) * | 2016-07-01 | 2022-05-03 | Evolve Biosystems, Inc. | Method for facilitating maturation of the mammalian immune system |
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KR20240016454A (en) | 2024-02-06 |
AU2017318386A1 (en) | 2019-03-21 |
CA3035290A1 (en) | 2018-03-08 |
US20190183145A1 (en) | 2019-06-20 |
AU2022204538A1 (en) | 2022-07-21 |
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